Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
J Cell Sci. 2021 Oct 1;134(19). doi: 10.1242/jcs.240465. Epub 2021 Oct 6.
Mitochondria, which resemble their α-proteobacteria ancestors, are a major cellular asset, producing energy 'on the cheap' through oxidative phosphorylation. They are also a liability. Increased oxidative phosphorylation means increased oxidative stress, and damaged mitochondria incite inflammation through release of their bacteria-like macromolecules. Mitophagy (the selective macroautophagy of mitochondria) controls mitochondria quality and number to manage these risky assets. Parkin, BNIP3 and NIX were identified as being part of the first mitophagy pathways identified in mammals over a decade ago, with additional pathways, including that mediated by FUNDC1 reported more recently. Loss of Parkin or PINK1 function causes Parkinson's disease, highlighting the importance of mitophagy as a quality control mechanism in the brain. Additionally, mitophagy is induced in idiopathic Parkinson's disease and Alzheimer's disease, protects the heart and other organs against energy stress and lipotoxicity, regulates metabolism by controlling mitochondrial number in brown and beige fat, and clears mitochondria during terminal differentiation of glycolytic cells, such as red blood cells and neurons. Despite its importance in disease, mitophagy is likely dispensable under physiological conditions. This Review explores the in vivo roles of mitophagy in mammalian systems, focusing on the best studied examples - mitophagy in neurodegeneration, cardiomyopathy, metabolism, and red blood cell development - to draw out common themes.
线粒体类似于它们的α-变形菌祖先，是一种主要的细胞资产，通过氧化磷酸化“廉价”地产生能量。它们也是一种负担。氧化磷酸化的增加意味着氧化应激的增加，受损的线粒体通过释放类似细菌的大分子引发炎症。线粒体自噬（线粒体的选择性巨自噬）控制线粒体的质量和数量，以管理这些有风险的资产。Parkin、BNIP3 和 NIX 被确定为十多年前在哺乳动物中首次鉴定的线粒体自噬途径的一部分，最近又报道了其他途径，包括由 FUNDC1 介导的途径。Parkin 或 PINK1 功能的丧失会导致帕金森病，这突显了线粒体自噬作为大脑中质量控制机制的重要性。此外，在特发性帕金森病和阿尔茨海默病中诱导线粒体自噬，保护心脏和其他器官免受能量应激和脂肪毒性的影响，通过控制棕色和米色脂肪中的线粒体数量来调节代谢，在糖酵解细胞（如红细胞和神经元）的终末分化过程中清除线粒体。尽管它在疾病中的重要性，但在生理条件下，线粒体自噬可能是可有可无的。这篇综述探讨了线粒体自噬在哺乳动物系统中的体内作用，重点研究了研究最深入的例子——神经退行性变、心肌病、代谢和红细胞发育中的线粒体自噬，以得出共同的主题。
